DOB: - GX Sciencesgxsciences.com/v/vspfiles/downloadables/Neuro_Psych... · 2018-12-19 · Neurological / Psych Neurotransmitters rs4680 COMT V158M +/+ Taurine, Choline, Trimethylglycine

Gene Comprehensive Nutrigenomic Report

Accession Number: ###########

Report Generated: December 13, 2018

Specimen Received: ##/##/####

Created For: ###### ######

DOB: ##/##/####

Male

Do not make any decisions about your health solely based on the information contained in this report.Always consult with a licensed and experienced health practitioner when you receive this report.

REDACTED - 95108110-820f-4136-bc3e-d063b1ec540c 1 December 13, 2018

Neurological / PsychGX Sciences | 844-258-5564 | www.GXSciences.com

Lab | 4150 Freidrich Lane, Ste H | Austin, TX 78744Laboratory Director: James W. Jacobson, Ph.D

###### ###### – 34 – Male (-/-) No clinical abnormality (+/-) Heterozygous result (+/+) Homozygous result

rsID GeneGeneticResult

Therapeutics Associated WithPositive Result

Highly Recommended Therapeutics/ Neurobiologix Formulas

Provider Discretion:As Needed FormulaRecommendations

LifestyleRecommendations

LaboratoryRecommendations

Neurological / Psych

Neurotransmitters

rs4680COMTV158M

+/+ Taurine, Choline, Trimethylglycine (TMG), Dimethylglycine (DMG),

Methionine, SAMe, InositolFull Focus+TM

Consider Neurotransmitter Metabolite Testing and

PGx Testingrs4633COMTH62H

+/+

rs769407 GAD1 +/- Prescription Amantadine, Ketamine, Glycine, N-Acetyl-Cysteine (NAC), Beta Phenyl

GABA, Zinc, Magnesium, Oxaloacetate, Elderberry, L-

Theanine, Melatonin

Pro GAD EnhancerTM, Prescription Amantadine

Pro GAD EnhancerTM, Melatonin, Calming CreamTM, Prescription

Amantadine, Ketamine

Be cautious with MSG (monosodium glutamate)

and glutamine supplementation

Consider Neurotransmitter Testing and PGx Testing

rs3828275 GAD1 +/-

rs6323 MAO-A +/NA B2 (Riboflavin), Methyl Donors (Taurine, Choline, Trimethylglycine

(TMG), Dimethylglycine (DMG), Inositol, Methioniners1799836 MAO-B -/NA

rs6313 HTR2 +/-

5-HTP (Hydroxytryptophan)

rs1042173 SLC6A4 -/-












Neuro-Inflammation

rs10402876 C3 +/-

Anti-Inflammatory Therapy: Curcumin, Omega 3s, Resveratrol, Quercetin, Low Dose Naltrexone

(LDN), CBD Oil

CBD Oil, PEA Soothe SupportTM

, Prescription Low Dose Naltrexone (LDN)

Consider Low Inflammatory Diet

Consider Pregnenolone, Cortisol, Progesterone,

Testosterone, T cell profile, Sed Rate, ANA, C Reactive Protein, Routine Thyroid Panel, Candida Titer, EBV Titer, Food

Allergy Panel, Environmental Allergy

Testing

rs2569191 CD14 +/-

rs1143634 IL1B -/-

rs1800795 IL6 +/+

rs2069812 IL5 +/-

rs1800925 IL13 -/-

rs10181656 STAT4 +/+

rs1800629 TNF -/-

rs361525 TNF -/-

rs231775 CTLA4 +/-

rs1076560 DRD2 -/- Increased Efficacy of Naltrexone












Autophagy Efficacy

rs10210302 ATG16L1 +/-

Curcumin, Lithium Orotate, D-Chiro-Inositol, Catechins, Resveratrol,

Caffeine, 12 Hour Fasting

N.A.S. EnhancerTM

(NRF2|Autophagy|SOD Support), Metabolic StimulatorTM

Calorie Restriction, 12-15 Hour Fasting

Routine Blood Sugar, Insulin and Hb A1c

rs26538 ATG12 +/+

rs510432 ATG5 +/-

rs1007008 SMURF1 -/-

rs104893875PARK1(alpha

synuclein)-/-

Curcumin, Lithium Orotate, D-Chiro-Inositol, Catechins, Resveratrol,

Caffeine, 12-15 Hour Fasting

N.A.S. EnhancerTM

(NRF2|Autophagy|SOD Support), Metabolic StimulatorTM, mTOR

Inhibitors

Increased Risk of Parkinson's, Calorie

Restriction, 12-15 Hour Fasting

rs3798963PARK2(Parkin)

+/-

rs45478900PARK6(PINK1)

-/-

rs429358 APOE -/- Calorie Restriction, Routine 12-15 Hour Fasting, Increased Risk of

Memory Disordersrs7412 APOE -/-

Detoxification

rs1021737 CTH -/-N-Acetyl Cysteine (NAC),

Glutathioners819147 AHCY -/-

rs7483 GSTM3 +/- GlutathioneGlutathione IV, Glutathione

Suppositories, Glutathione UltraTM, Glutathione Plus TopicalTM

Consider IV Glutathione Treatment and Pre-

Anesthesia Glutathione Treatment; Herbicide and

Pesticide Avoidance


Summary for Neurological / Psych

Highly Recommended Therapeutics / Neurobiologix Formulas

Lifestyle Recommendations Laboratory Recommendations

• Full Focus+TM

• Pro GAD EnhancerTM, Prescription Amantadine

•CBD Oil, PEA Soothe SupportTM, Prescription Low Dose Naltrexone (LDN)

•N.A.S. EnhancerTM (NRF2|Autophagy|SOD Support), Metabolic StimulatorTM

•Be cautious with MSG (monosodium glutamate) and glutamine supplementation

• Consider Low Inflammatory Diet

• Calorie Restriction, 12-15 Hour Fasting

•Increased Risk of Parkinson's, Calorie Restriction, 12-15 Hour Fasting

•Consider IV Glutathione Treatment and Pre-Anesthesia Glutathione Treatment; Herbicide and Pesticide Avoidance

• Consider Neurotransmitter Metabolite Testing and PGx Testing

• Consider Neurotransmitter Testing and PGx Testing

•

Consider Pregnenolone, Cortisol, Progesterone, Testosterone, T cell profile, Sed Rate, ANA, C Reactive Protein, Routine Thyroid Panel, Candida Titer, EBV Titer, Food Allergy Panel, Environmental Allergy Testing

• Routine Blood Sugar, Insulin and Hb A1c



Gene Information Key

rsID Gene"-"

variant"+"

variant

rs819147 AHCY T C

rs7412 APOE C T

rs429358 APOE T C

rs26538 ATG12 T C

rs10210302 ATG16L1 C T

rs510432 ATG5 C T

rs10402876 C3 G C

rs2569191 CD14 T C

rs4633 COMT H62H C T

rs4680 COMT V158M G A

rs1021737 CTH G T

rs231775 CTLA4 A G

rs1076560 DRD2 C A

rs3828275 GAD1 C T

rs769407 GAD1 G C

rs7483 GSTM3 C T

rs6313 HTR2 G A

rsID Gene"-"

variant"+"

variant

rs1800925 IL13 C T

rs1143634 IL1B G A

rs2069812 IL5 A G

rs1800795 IL6 G C

rs6323 MAO-A T G

rs1799836 MAO-B T C

rs104893875 PARK1 (alpha synuclein) C T

rs3798963 PARK2 (Parkin) A T

rs45478900 PARK6 (PINK1) G A

rs1042173 SLC6A4 A C

rs1007008 SMURF1 C T

rs10181656 STAT4 C G

rs361525 TNF G A

rs1800629 TNF G A


Definitions

DETOXIFICATIONDetoxification enzymes are responsible for clearing environmental chemicals and metabolites from our body. Accumulation of these chemicals and by-products can damage intracellular biochemical functions. Alterations in these systems can have a significant negative effect on the nervous system and immune systems functions. These polymorphisms can result in decreased "quality of life" and even decreased "life-span".

AHCYAdenosylhomocysteinase (AHCY) is an enzyme that breaks down S-adenosylhomocysteine (SAH) to homocysteine and adenosine. Polymorphisms in this gene will lead to lower levels of homocysteine and glutathione.

CTHGlutathione production is dependent on the function of the enzyme cystathionine gamma-lyase (CTH). CTH converts cystathionine to cysteine. Individuals with mutations in the CTH gene are predicted to have decreased glutathione-mediated detoxification.

GSTM3Glutathione S-transferase mu 3 is an enzyme that detoxifies drugs, environmental toxins, and carcinogens by conjugating toxins to glutathione and subsequent excretion by the kidneys. Mutations in GSTM3 are associated with decreased clearance of toxins, anesthetics and drugs from the nervous system.

DEVELOPMENTAL

APOE: 130 Individuals homozygous for the C/C allele at rs429358 may harbor the APOE E4 allele. Consult with a provider to determine APOE risk allele status.

APOE: Arg176CysIndividuals homozygous for T/T at rs7412 are assumed to have the E2 allele of the gene APOE. APOE encodes a protein involved in cholesterol and lipid transport and metabolism

ATG12Autophagy-related 12 protein is part of the core autophagy machinery inside the cell. Autophagy, a form of cellular "recycling" is necessary for many cell functions. ATG12 is specifically involved in turning off the innate immune response. Mutations in the ATG12 gene are predicted to lead to increased activity of the innate immune response, and overall inflammation.

PARK1PARK1, also known as alpha synuclein, is a highly expressed protein in neurons. Mutations in the PARK1 gene are associated with increased risk of neurodegenerative disorders such as parkinsonism.

PARK2 PARK2 is a protein involved in normal turnover of damaged or old proteins inside the cell. Mutations in the PARK2 gene are associated with heritable Parkinson's disease.

PARK6 The PARK6 protein, also known as PINK1, is a mitochondrial protein kinase. Mutations in PARK6 are associated with autosomal recessive Parkinson's disease.

SMURF-1The SMURF1 protein is a negative regulator of pathways involved in cell polarity, growth, and differentiation. Normal function of the SMURF1 protein is required for normal development and innate immune function. Polymorphisms in this gene can significantly affect autophagy performance of the cell.

INFLAMMATORYThis enzyme category has significant effects on the inflammatory state of a person's body. Polymorphisms in these specific enzymes will significantly increase the levels of inflammation in the body. By supplementing these enzyme deficiencies, the patient will effectively reduce inflammatory damage to the body.

ATG16L1The ATG16L1 gene encodes a protein that is a vital component of a protein complex necessary for the cellular phenomena known as autophagy. Autophagy is the process of degrading and cleaning of inert debris of the cell. Weakness in autophagy leads to abnormal accumulation of cellular “garbage” that will eventually affect the cellular function and lead to autophagy related disease states in including many neurological and immunological diseases, DM Type 2 and fatty liver disease.

ATG5Autophagy-related 5 protein (ATG5) is an important intracellular mediator of the autophagy response. ATG5 is involved in a wide range of "quality control" features inside the cell: autophagy vesicle formation, innate immune system signaling, consumption of damaged mitochondria, and apoptosis. Mutations in the ATG5 gene are associated with numerous neurological, immunological and endocrine syndromes.

C3Essential for the immune response, C3 is a protein involved in initiation of the complement system. C3 polymorphisms are associated with susceptibility to asthma and other inflammatory disorders.

CD14The CD14 protein is a macrophage cell surface receptor that binds bacterial cell wall components. As one of the initiators of the innate immune response, fully functional CD14 is necessary for normal response to potential pathogens. Mutations in the CD14 gene are associated with susceptibility to asthma and other allergen-mediated inflammatory processes.

CTLA4Cytotoxic T-lymphocyte Associated protein 4 (CTLA4) is an important inhibitor of T-cell activity: CTLA4 is part of the signaling cascade that turns off overactive T cells. Mutations in the gene that encodes CTLA4 are associated with a host of diseases characterized by a heightened immune state.

DRD2Dopamine receptor D2 is an important component of the neuroinflammation process. Activation of DRD2 signaling is thought to decrease TNFalpha release from inflammatory mast cells. Polymorphisms associated with decreased DRD2 signaling activity are predicted to lead to pro-inflammatory phenotypes.

IL13IL13 (Interleukin 13) is a member of the interleukin family of chemical messengers of the immune system. Polymorphisms in this gene are associated with changes in IL13 gene expression and increase the risk of more severe inflammatory responses to allergens.


IL5The protein product of the Interleukin 5 gene (IL5) is important for normal development of B lymphocytes and eosinophils (a pro-inflammatory white blood cell). Inactivating mutations in the IL5 gene are associated with susceptibility to certain viral infections and increased aggression of inflammatory response. These polymorphisms are also associated with increased aggression of allergies, asthma and eosinophilia.

IL6Interleukin 6, IL6, is an important pro-inflammatory cytokine. Polymorphisms in this gene leads to a more aggressive inflammatory response. Patients with IL-6 mutations require assistance with inflammatory control.

STAT4The Signal Transducer and Activator of Transcription 4 (STAT4) gene encodes a transcription factor that responds to extracellular growth factors and cytokines. Mutations in the STAT4 gene are associated with inflammatory disorders like lupus and rheumatoid arthritis.

TNFTumor necrosis factor, TNF, is an important pro-inflammatory signaling molecule. Polymorphisms in the protein coding part of this gene are associated with more severe pro-inflammatory responses and require supplementation for inflammatory control.

NEUROTRANSMITTERNeurotransmitters are chemicals that are used to produce specific effects in the nervous system. These specific neurotransmitter genomics assess a person's risk for anxiety, depression and dysphoria.

COMT H62H

Catechol-O-methyltransferase (COMT) is one of several enzymes that degrade catecholamine neurotransmitters such as dopamine, epinephrine, and norepinephrine. COMT's main function is to inactivate neurotransmitters (dopamine, epinephrine, and norepinephrine) by the addition of a methyl group to the catecholamine. Normal COMT function allows people to rapidly reverse feelings of anxiety or depression. COMT (+/-) patients have sluggish ability to alter anxiety or depression episodes. COMT (+/+) patients are more prone to prolonged episodes of anxiety, depression and OCD.

COMT V158M

Catechol-O-methyltransferase (COMT) is one of several enzymes that degrade catecholamine neurotransmitters such as dopamine, epinephrine, and norepinephrine. COMT's main function is to inactivate neurotransmitters (dopamine, epinephrine, and norepinephrine) by the addition of a methyl group to the catecholamine. Normal COMT function allows people to rapidly reverse feelings of anxiety or depression. COMT (+/-) patients have sluggish ability to alter anxiety or depression episodes. COMT (+/+) patients are more prone to prolonged episodes of anxiety, depression and OCD.

GAD1Glutamic Acid Decarboxylase (GAD 1) is the enzyme responsible for conversion of glutamic acid (a stimulant neurotransmitter) to GABA (a calming neurotransmitter). Deficiency of GABA from polymorphisms in this enzyme are associated with sleep disorders, "half glass empty" syndrome, dysphoria, and spasticity.

HTR25-hydroxytryptamine receptor 2 (HTR2) is one of the neuronal receptors for the neurotransmitter serotonin. Mutations in the HTR2 gene are associated with individual response to antidepressants, appetite, and mood.

IL1BInterleukin 1B is the pro-inflammatory cytokine responsible for inducing cyclooxygenase-2 (COX2) expression in the central nervous system. COX2 enzymatic function leads to prostanoid signaling that increases pain sensation associated with inflammation. Mutations in the IL1B gene are associated with many chronic inflammation disorders.

MAO-AMonoamine oxidase A (MAOA) is one of the classic neurotransmitter degradation enzymes. By degrading serotonin, dopamine, epinephrine, and norepinephrine, MAO-A ends neuronal signaling induced by those neurotransmitters. Mutations in the MAO-A gene leads to decreased degradation of these neurotransmitters and can be associated with increased aggression, mood disorders and drug addiction.

MAO BMonoamine Oxidase B (MAO B) catalyzes the neuroactive amines, such as dopamine, epinephrine, norepinephrine, and plays a role in the stability of mood in the central nervous system,. MAO B's primary purpose is to degrade dopamine. Patients who possess polymorphisms of MAO B have a higher risk of clinical depression and mood disorders.

SLC6A4The SLC6A4 gene encodes the serotonin transporter, also known as SERT. The serotonin transporter is responsible for clearing the serotonin neurotransmitter from the synaptic space. SERT is the target of many therapeutic drugs. Polymorphisms in the SLC6A4 gene are associated with increased risk of anxiety and depression and less effective response to SSRI medications.


DisclaimersMETHODOLOGY AND LIMITATIONS:

Testing for genetic variation/mutation on listed genes was performed using ProFlex PCR and Real-Time PCR with TaqMan® allele-specific probes on the QuantStudio 12K Flex. All genetic testing is performed by GX Sciences, 4150 Freidrich Lane, Ste H, Austin, TX. 78744. This test will not detect all the known alleles that result in altered or inactive tested genes. This test does not account for all individual variations in the individual tested. Test results do not rule out the possibility that this individual could be a carrier of other mutations/variations not detected by this gene mutation/variation panel. Rare mutations surrounding these alleles may also affect our detection of genetic variations. Thus, the interpretation is given as a probability. Therefore, this genetic information shall be interpreted in conjunction with other clinical findings and familial history for the administration of specific nutrients. Patients should receive appropriate genetic counseling to explain the implications of these test results. Details of assay performance and algorithms leading to clinical recommendations are available upon request. The analytical and performance characteristics of this laboratory developed test (LDT) were determined by GX Sciences’ laboratory pursuant to Clinical Laboratory Improvement Amendments (CLIA) requirements.CLIA #: 45D2144988

DISCLAIMER:

This test was developed and its performance characteristics determined by GX Sciences. It has not been cleared or approved by the FDA. The laboratory is regulated under CLIA and qualified to perform high-complexity testing. This test is used for clinical purposes. It should not be regarded as investigational or for research. rsIDs for the alleles being tested were obtained from the dbSNP database (Build 142).

DISCLAIMER:

UND Result: If you have received the result Variant undetermined (UND) this indicates that we were not able to determine your carrier status based on your raw data. Please refer to the GX Sciences genetic knowledge database for more information: https://www.gxsciences.com/kb_results.asp

DISCLAIMER:

Report contents and report recommendations are created and approved by GX Sciences. Sole responsibility for the proper use of the information on the GX Sciences report rests with the user, or those professionals with whom the user may consult. Nutrigenomic Testing and Neurobiologix Dietary Supplements are not “Designated Health Services” covered by Medicare or Medicaid and may not be reimbursed under any state or Federal health care program.

DISCLAIMER:

These products are not approved by the Food and Drug Administration and are not intended to diagnose, treat, cure or prevent a disease. These recommendations are for report purposes only and an individual is not required to use such products. These are recommendations only and do not replace the advisement of your own healthcare practitioner.


GX Sciences SNP References

DETOXIFICATION SNP References

AHCY

• Vugrek, O., Beluži?, R. & Naki?, N. S-adenosylhomocysteine hydrolase (AHCY) deficiency: Two novel mutations with lethal outcome. Hum. Mutat. 30, (2009). • Motzek, A. et al. Abnormal hypermethylation at imprinting control regions in patients with S-adenosylhomocysteine hydrolase (AHCY) deficiency. PLoS One 11, (2016).

CTH

• Wang, J. & Hegele, R. a. Genomic basis of cystathioninuria (MIM 219500) revealed by multiple mutations in cystathionine gamma-lyase (CTH). Hum. Genet. 112, 404–408 (2003). • Huezo-Diaz, P. et al. Association of Cth genetic variant with veno-occlusive disease in children receiving intravenous busulfan before hematopoietic

stem cell transplantation. Blood 120, (2012).

GSTM3

• Maes, O. C., Schipper, H. M., Chong, G., Chertkow, H. M. & Wang, E. A GSTM3 polymorphism associated with an etiopathogenetic mechanism in Alzheimer disease. Neurobiol. Aging (2010). doi:10.1016/j.neurobiolaging.2008.03.007 • Patskovsky, Y. V, Huang, M. Q., Takayama, T., Listowsky, I. & Pearson, W. R. Distinctive

structure of the human GSTM3 gene-inverted orientation relative to the mu class glutathione transferase gene cluster. Arch. Biochem. Biophys. (1999). doi:10.1006/abbi.1998.0964

DEVELOPMENTAL SNP References

APOE: 130

• Takei, N. et al. Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese. Genomics 93, 441–448 (2009). • Tejedor, M. T., Garcia-Sobreviela, M. P., Ledesma, M. & Arbones-Mainar, J. M. The apolipoprotein E polymorphism rs7412 associates with body fatness independently of plasma lipids

in middle aged men. PLoS One 9, e108605 (2014). • Rubinsztein, D. C. & Easton, D. F. Apolipoprotein E Genetic Variation and Alzheimer’s Disease. Dement. Geriatr. Cogn. Disord. 10, 199–209 (1999).

APOE: Arg176Cys

• Ruaño, G. et al. Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients. Mol. Psychiatry 12, 474–482 (2007). • Tejedor, M. T., Garcia-Sobreviela, M. P., Ledesma, M. & Arbones-Mainar, J. M. The apolipoprotein E polymorphism rs7412 associates with body fatness independently of plasma lipids

in middle aged men. PLoS One 9, e108605 (2014).

ATG12

• Anton, R. F. et al. Pharmacogenomics. Nat. Genet. 16, 268–278 (2008). • Yuan, J. et al. Polymorphisms in autophagy related genes and the coal workers’ pneumoconiosis in a Chinese population. Gene 632, 36–42 (2017).

PARK1

• Jiang, L. et al. PARK1 gene mutation of autosomal dominant Parkinson’s disease family. Neural Regen. Res. 6, 330–334 (2011). • Brookes, A. J. The essence of SNPs. Gene 234, 177–186 (1999).

PARK2

• Benitez, B. A. et al. Resequencing analysis of five Mendelian genes and the top genes from genome-wide association studies in Parkinson’s Disease. Mol. Neurodegener. 11, 29 (2016). • Xu, L., Lin, D., Yin, D. & Koeffler, H. P. An emerging role of PARK2 in cancer. J. Mol. Med. 92, 31–42 (2014).

PARK6

• Khan, N. L. et al. Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: An18F-dopa PET study. Ann. Neurol. 52, 849–853 (2002). • Clarimón, J. et al. Assessment of PINK1 (PARK6) polymorphisms in Finnish PD. Neurobiol. Aging 27, 906–907 (2006).

SMURF1

• Yuan, C., Qi, J., Zhao, X. & Gao, C. Smurf1 protein negatively regulates interferon-$?$ signaling through promoting STAT1 protein ubiquitination and degradation. J. Biol. Chem. 287, 17006–17015 (2012).

INFLAMMATORY SNP References

ATG16L1

• Begun, J. et al. Integrated Genomics of Crohn’s Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy. Cell Rep. (2015). doi:10.1016/j.celrep.2015.05.045 • Messer, J. S. et al. The Crohn’s disease: Associated ATG16L1 variant and Salmonella invasion. BMJ Open (2013). doi:10.1136/bmjopen-2013-002790 • Boada-Romero, E. et al. The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1. Nat. Commun. (2016). doi:10.1038/ncomms11821 • Lassen, K. G. et al. Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense. Proc.


Natl. Acad. Sci. (2014). doi:10.1073/pnas.1407001111 • Kabat, A. M. et al. The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation. Elife (2016). doi:10.7554/eLife.12444 • Cheng, J. F., Ning, Y. J., Zhang, W., Lu, Z. H. & Lin, L. T300A polymorphism of ATG16L1 and susceptibility to inflammatory bowel diseases: A meta-analysis. World J. Gastroenterol. (2010). doi:10.3748/wjg.v16.i10.1258 • Salem, M., Ammitzboell, M., Nys, K., Seidelin, J. B. & Nielsen, O. H. ATG16L1: A multifunctional susceptibility factor in crohn disease. Autophagy (2015). doi:10.1080/15548627.2015.1017187 • Salem, M., Nielsen, O. H., Nys, K., Yazdanyar, S. & Seidelin, J. B. Impact of T300A Variant of ATG16L1 on antibacterial response, risk of culture positive infections, and clinical course of Crohn’s disease. Clin. Transl. Gastroenterol. (2015). doi:10.1038/ctg.2015.47 • Gazouli, M. et al. NOD2/CARD15, ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn’s disease. World J. Gastroenterol. (2010). doi:10.3748/wjg.v16.i14.1753 • Kuballa, P., Huett, A., Rioux, J. D., Daly, M. J. & Xavier, R. J. Impaired autophagy of an intracellular pathogen induced by a Crohn’s disease associated ATG16L1 variant. PLoS One (2008). doi:10.1371/journal.pone.0003391 • Rosentul, D. C. et al. Role of autophagy genetic variants for the risk of Candida infections. Med. Mycol. (2014). doi:10.1093/mmy/myt035 • Raju, D., Hussey, S. & Jones, N. L. Crohn disease ATG16L1 polymorphism increases susceptibility to infection with Helicobacter pylori in humans. Autophagy (2012). doi:10.4161/auto.21007 • Stappenbeck, T. S. et al. Crohn disease: A current perspective on genetics, autophagy and immunity. Autophagy (2011). doi:10.4161/auto.7.4.13074 • Csöngei, V. et al. Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients. World J. Gastroenterol. (2010). doi:10.3748/wjg.v16.i2.176 • Usategui-Martín, R. et al.

Polymorphisms in autophagy genes are associated with paget disease of bone. PLoS One (2015). doi:10.1371/journal.pone.0128984 • Glubb, D. M. et al. NOD2 and ATG16L1 polymorphisms affect monocyte responses in crohn’s disease. World J. Gastroenterol. (2011). doi:10.3748/wjg.v17.i23.2829

ATG5

• Yuan, J. et al. Polymorphisms in autophagy related genes and the coal workers’ pneumoconiosis in a Chinese population. Gene 632, 36–42 (2017). • White, K. A. M. et al. Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study. Cancer Med. 5, 3336–3345 (2016). • Anton, R. F. et al.

Pharmacogenomics. Nat. Genet. 16, 268–278 (2008). • Martin, L. J. et al. Functional Variant in the Autophagy-Related 5 Gene Promotor is Associated with Childhood Asthma. PLoS One 7, e33454 (2012).

C3

• Li, Y., Li, C. & Gao, J. Apolipoprotein C3 gene variants and the risk of coronary heart disease: A meta-analysis. Meta Gene (2016). doi:10.1016/j.mgene.2016.04.004 • Rasheed, H. et al. Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout. Rheumatol. (United Kingdom) (2016). doi:10.1093/rheumatology/kew057 • Bonyadi, M. et al. Association of polymorphisms in complement component 3 with age-related macular degeneration in an Iranian population. Ophthalmic Genet. (2016). doi:10.3109/13816810.2015.1126612 • Nsaiba, M. J. et al. C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients. Neurochem. Res. (2015). doi:10.1007/s11064-015-1543-z • Prechl, J. et al. Serological and genetic evidence for altered complement system functionality in systemic lupus erythematosus: Findings of the GAPAID consortium. PLoS One (2016). doi:10.1371/journal.pone.0150685 • Wu, Y. et al. Interactions of environmental factors and APOA1-APOC3-APOA4-APOA5 gene cluster gene polymorphisms with metabolic syndrome. PLoS One (2016). doi:10.1371/journal.pone.0147946 • Saksens, N. T. M. et al. Rare Genetic Variants Associated With Development of Age-Related Macular Degeneration. JAMA Ophthalmol.

(2016). doi:10.1001/jamaophthalmol.2015.5592 • Wu, W. et al. Polymorphisms in complement genes and risk of preeclampsia in Taiyuan, China. Inflamm. Res. (2016). doi:10.1007/s00011-016-0968-4

CD14

• Zhang, A. Q. et al. Association between CD14 promoter -159C/T polymorphism and the risk of sepsis and mortality: a systematic review and meta-analysis. PloS one (2013). doi:10.1371/journal.pone.0071237 • Loo, W. T. Y. et al. Clinical application of human ?-defensin and CD14 gene polymorphism in evaluating the status of chronic inflammation. J. Transl. Med. (2012). doi:10.1186/1479-5876-10-S1-S9 • Misra, S. et al. Genetic association between inflammatory genes (IL-1?, CD14, LGALS2, PSMA6) and risk of ischemic stroke: A meta-analysis. Meta Gene (2016). doi:10.1016/j.mgene.2016.01.003 • Areeshi, M. Y., Mandal, R. K., Panda, A. K., Bisht, S. C. & Haque, S. CD14 -159 C>T Gene Polymorphism with Increased Risk of Tuberculosis: Evidence from a Meta-Analysis. PLoS One (2013). doi:10.1371/journal.pone.0064747 • Kim, E. J. et al. Helicobacter pylori infection enhances gastric mucosal inflammation in individuals carrying the 260-T allele of the CD14 gene. Gut Liver (2013). doi:10.5009/gnl.2013.7.3.317 • Wang, J. et al. Association between CD14 gene polymorphisms and cancer risk: A meta-analysis. PLoS One (2014). doi:10.1371/journal.pone.0100122 • Wang, S. et al. Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity. J. Asthma Allergy (2013). doi:10.2147/JAA.S42695 • Wang, Z., Hu, J., Fan, R., Zhou, J. & Zhong, J. Association between CD14 Gene C-260T Polymorphism and Inflammatory Bowel Disease: A Meta-Analysis. PLoS One (2012). doi:10.1371/journal.pone.0045144 • Cheah, M. T. et al. CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer. Proc. Natl. Acad. Sci. (2015). doi:10.1073/pnas.1424795112 • Liu, B. et al. CD14 ++ CD16 + Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses. J. Immunol. (2015).

doi:10.4049/jimmunol.1402409

CTLA4

• Patel, H. et al. Association of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) genetic variants with autoimmune hypothyroidism. PLoS One (2016). doi:10.1371/journal.pone.0149441 • Liu, J. & Zhang, H.-X. CTLA-4 polymorphisms and systemic lupus erythematosus: a comprehensive meta-analysis. Genet. Test. Mol. Biomarkers (2013). doi:10.1089/gtmb.2012.0302 • Orrù, S. et al. Recipient CTLA-4*CT60-AA genotype is a prognostic factor for acute graft-versus-host disease in hematopoietic stem cell transplantation for thalassemia. Hum. Immunol. (2012). doi:10.1016/j.humimm.2011.12.014 • Wang, D. C., Tan, B. Y., Wang, F. & Yuan, Z. N. Association between CTLA-4 gene polymorphism and ankylosing spondylitis: A case-control study. Int. J. Clin. Exp. Pathol. (2015). • Jeffery, L. E. et al. Vitamin D antagonises the suppressive effect of inflammatory cytokines on CTLA-4 expression and regulatory function. PLoS One (2015). doi:10.1371/journal.pone.0131539 • Bour-Jordan, H. et al. Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family. Immunol. Rev. (2011). doi:10.1111/j.1600-065X.2011.01011.x • Tector, M., Khatri, B. O., Kozinski, K., Dennert, K. & Oaks, M. K. Biochemical analysis of CTLA-4 immunoreactive material from human blood. BMC Immunol. (2009). doi:10.1186/1471-2172-10-51 • Karabon, L. et al. The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease. Immunology (2009). doi:10.1111/j.1365-2567.2009.03083.x • AlFadhli, S. Overexpression and Secretion of the Soluble CTLA-4 Splice Variant in Various Autoimmune Diseases and in Cases with Overlapping Autoimmunity. Genet. Test. Mol. Biomarkers (2013). doi:10.1089/gtmb.2012.0391 • Wolff, A. S. B. et al. CTLA-4 as a genetic determinant in autoimmune Addison’s disease. Genes Immun. (2015). doi:10.1038/gene.2015.27 • Zaletel, K. et al. Association of CT60 cytotoxic T lymphocyte antigen-4 gene polymorphism with thyroid autoantibody production in patients with Hashimoto’s and postpartum thyroiditis. Clin. Exp. Immunol. (2010). doi:10.1111/j.1365-2249.2010.04113.x • Abdel Galil, S. M. & Hagrass, H. A. The role of CTLA-4 exon-1 49 A/G polymorphism and soluble CTLA-4 protein level in Egyptian patients with Behçet’s disease. Biomed Res. Int. (2014). doi:10.1155/2014/513915 • Du, L. et al. The associations between the polymorphisms in the CTLA-4 gene and the risk of Graves’ disease in the Chinese population. BMC Med. Genet. (2013). doi:10.1186/1471-2350-14-46 • Esposito, L. et al. Investigation of Soluble and Transmembrane CTLA-4 Isoforms in Serum and Microvesicles. J. Immunol. (2014). doi:10.4049/jimmunol.1303389 • Walker, L. S. K. Treg and CTLA-4: Two intertwining pathways to immune tolerance. Journal of Autoimmunity (2013). doi:10.1016/j.jaut.2013.06.006 • Zhao, J. J., Wang, D., Yao, H., Sun, D. W. & Li, H. Y. CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis. World J. Gastroenterol. (2015). doi:10.3748/wjg.v21.i34.10025 • Nie, W., Chen, J. & Xiu, Q. Cytotoxic T-lymphocyte associated antigen 4 polymorphisms and asthma risk: A meta-analysis. PLoS One (2012). doi:10.1371/journal.pone.0042062 • Wang, J. et al. Common variants on cytotoxic T lymphocyte antigen-4 polymorphisms contributes to type 1 diabetes susceptibility: Evidence based on 58 studies. PLoS One (2014). doi:10.1371/journal.pone.0085982 • Yan, Q., Chen, P., Lu, A., Zhao, P. & Gu, A. Association between CTLA-4

60G/A and -1661A/G polymorphisms and the risk of cancers: A meta-analysis. PLoS One (2013). doi:10.1371/journal.pone.0083710

DRD2

• Clarke, T. K. et al. The dopamine receptor D2 (DRD2) SNP rs1076560 is associated with opioid addiction. Ann. Hum. Genet. (2014). doi:10.1111/ahg.12046 • Anton, R. F. et al. Pharmacogenomics. Nat. Genet. (2008). doi:10.1016/j.ejca.2015.06.122 • Sasabe, T., Furukawa, A., Matsusita, S., Higuchi, S. & Ishiura, S. Association

analysis of the dopamine receptor D2 (DRD2) SNP rs1076560 in alcoholic patients. Neurosci. Lett. (2007). doi:10.1016/j.neulet.2006.10.064

IL-13

• Blanchard, C. Molecular pathogenesis of eosinophilic esophagitis. Curr. Opin. Gastroenterol. (2015). doi:10.1097/MOG.0000000000000186 • Seyfizadeh, N. et al. Association of IL-13 single nucleotide polymorphisms in Iranian patients to multiple sclerosis. Am. J. Clin. Exp. Immunol. (2014). • Egli, A. et al. IL-28B is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza. PLoS Pathog. (2014). doi:10.1371/journal.ppat.1004556 • Liu, Z. et al. A meta-analysis of IL-13 polymorphisms and pediatric asthma risk. Medical science monitor : international medical journal of experimental and clinical research. (2014). Available at: https://www.ncbi.nlm.nih.gov/pubmed/25502839. • Cianferoni, A. & Spergel, J. M. From genetics to treatment of eosinophilic esophagitis. Current Opinion in Allergy and Clinical Immunology (2015). doi:10.1097/ACI.0000000000000200 • Narozna, B. et al. Polymorphisms in the interleukin 4, interleukin 4 receptor and interleukin 13 genes and allergic phenotype: A case control study. Adv. Med. Sci. (2016). doi:10.1016/j.advms.2015.07.003 • Shamran, H. A. et al. Single nucleotide polymorphisms in IL-10, IL-12p40, and IL-13 genes and susceptibility to glioma. Int. J. Med. Sci. (2015). doi:10.7150/ijms.12609 • Mitchel, J. A. et al. IL-13 Augments Compressive Stress–Induced Tissue Factor Expression in Human Airway Epithelial Cells. Am. J. Respir. Cell Mol. Biol. (2016). doi:10.1165/rcmb.2015-0252OC • Nicodemus-Johnson, J. et al. Genome-wide methylation study identifies an IL-13-induced epigenetic signature in asthmatic airways. Am. J. Respir. Crit. Care Med. (2016). doi:10.1164/rccm.201506-1243OC • Chen, P., Chen, C., Chen, K., Xu, T. & Luo, C. Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis. Tumor Biology (2014). doi:10.1007/s13277-014-2895-8 • Accordini, S. et al. An Interleukin 13 polymorphism is associated with symptom severity in adult subjects with ever asthma. PLoS One (2016). doi:10.1371/journal.pone.0151292 • Sonntag, K. et al. Chronic graft-versus-host-disease in CD34+-humanized NSG mice is associated with human susceptibility HLA haplotypes for autoimmune disease. J. Autoimmun. (2015). doi:10.1016/j.jaut.2015.06.006 • McCormick, S. M. & Heller, N. M.

Commentary: IL-4 and IL-13 receptors and signaling. Cytokine (2015). doi:10.1016/j.cyto.2015.05.023 • Gervas-Arruga, J. et al. The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease. PLoS One (2015). doi:10.1371/journal.pone.0126153

IL-5

• Burnham, M. E. et al. Cholesterol selectively regulates IL-5 induced mitogen activated protein kinase signaling in human eosinophils. PLoS One (2014). doi:10.1371/journal.pone.0103122 • Skrindo, I. et al. IL-5 production by resident mucosal allergen-specific T cells in an explant model of allergic rhinitis. Clin. Exp. Allergy (2015). doi:10.1111/cea.12543 • Turkeli, A. et al. IL-5, IL-8 and MMP -9 levels in exhaled breath condensate of atopic and nonatopic asthmatic children. Respiratory medicine. (2015). Available at: https://www.ncbi.nlm.nih.gov/pubmed/25937050. • Bafadhel, M. et al. Sputum IL-5 concentration is associated with a sputum eosinophilia and attenuated by corticosteroid therapy in COPD. Respiration (2009). doi:10.1159/000221902 • Molfino, N. A., Gossage, D., Kolbeck, R., Parker, J. M. & Geba, G. P. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clinical and Experimental Allergy (2012). doi:10.1111/j.1365-2222.2011.03854.x • Corren, J. Inhibition of interleukin-5 for the treatment of eosinophilic diseases. Discov. Med. (2012). • Schulten, V. et al. Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals. Proc. Natl. Acad. Sci. (2013). doi:10.1073/pnas.1300512110 • Larose, M. C. et al. Mechanisms of human eosinophil migration induced by the combination of IL-5 and the endocannabinoid 2-arachidonoyl-glycerol. Journal of Allergy and Clinical Immunology (2014). doi:10.1016/j.jaci.2013.12.1081 • Weber-Chrysochoou, C., Crisafulli, D., Kemp, A. S., Britton, W. J. & Marks, G. B. Allergen-specific IL-5 responses in

early childhood predict asthma at age eight. PLoS One (2014). doi:10.1371/journal.pone.0097995 • Silveira, A. et al. Plasma IL-5 concentration and subclinical carotid atherosclerosis. Atherosclerosis (2015). doi:10.1016/j.atherosclerosis.2014.12.046


IL6

• Anton, R. F. et al. Pharmacogenomics. Nat. Genet. (2008). doi:10.1016/j.ejca.2015.06.122 • Fishman, D. et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic- onset juvenile chronic arthritis. J. Clin. Invest. (1998). doi:10.1172/JCI2629 • Illig, T. et al. Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes. J. Clin. Endocrinol. Metab. (2004). doi:10.1210/jc.2004-0355 • Baumert, P., Lake, M. J., Stewart, C. E., Drust, B. & Erskine, R. M. Genetic variation and exercise-induced muscle damage: implications for athletic

performance, injury and ageing. European Journal of Applied Physiology (2016). doi:10.1007/s00421-016-3411-1 • Buxens, A. et al. Can we predict top-level sports performance in power vs endurance events? A genetic approach. Scand. J. Med. Sci. Sport. (2011). doi:10.1111/j.1600-0838.2009.01079.x

STAT4

• Glas, J. et al. Evidence for STAT4 as a common autoimmune gene: Rs7574865 is associated with colonic Crohn’s disease and early disease onset. PLoS One (2010). doi:10.1371/journal.pone.0010373 • Sigurdsson, S. et al. A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5. Hum. Mol. Genet. (2008). doi:10.1093/hmg/ddn184 • Namjou, B. et al. High-density genotyping of STAT4 reveals multiple haplotypic associations with Systemic lupus erythematosus in different racial groups. Arthritis Rheum. (2009). doi:10.1002/art.24387 • Sugiura, T. et al. Association between a C8orf13-BLK polymorphism and polymyositis/ dermatomyositis in the Japanese population: An additive effect with STAT4 on disease susceptibility. PLoS One (2014). doi:10.1371/journal.pone.0090019 • Gourh, P. et al. Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: Evidence of possible gene-gene interaction and alterations in Th1/Th2 cytokines. Arthritis Rheum. (2009). doi:10.1002/art.24958 • Lamana, A. et al. The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis. PLoS One (2012). doi:10.1371/journal.pone.0043661 • Yan, N. et al. Association between STAT4 Gene Polymorphisms and Autoimmune Thyroid Diseases in a Chinese Population. Int. J. Mol. Sci. (2014). doi:10.3390/ijms150712280 • Svensson, A. et al. STAT4 Regulates Antiviral Gamma Interferon Responses and Recurrent Disease during Herpes Simplex Virus 2 Infection. J. Virol. (2012). doi:10.1128/JVI.00947-12 • Wang, Y., Qu, A. & Qu, A. Signal transducer and activator of transcription 4 in liver diseases. International Journal of Biological Sciences (2015). doi:10.7150/ijbs.11164 • Lamana, A. et al. The minor allele of rs7574865 in the STAT4 gene is associated with increased mRNA and protein expression. PLoS One (2015). doi:10.1371/journal.pone.0142683 • McWilliams, I. L., Rajbhandari, R., Nozell, S., Benveniste, E. & Harrington, L. E. STAT4 controls GM-CSF production by both Th1 and Th17 cells during EAE. J. Neuroinflammation (2015). doi:10.1186/s12974-015-0351-3 • Jabeen, R. et al. Altered STAT4 Isoform Expression in

Patients with Inflammatory Bowel Disease. Inflamm. Bowel Dis. (2015). doi:10.1097/MIB.0000000000000495

TNF

• Laddha, N. C., Dwivedi, M., Gani, A. R., Mansuri, M. S. & Begum, R. Tumor Necrosis Factor B (TNFB ) genetic variants and its increased expression are associated with vitiligo susceptibility. PLoS One (2013). doi:10.1371/journal.pone.0081736 • Yang, J.-K., Wu, W.-J., Qi, J., He, L. & Zhang, Y.-P. TNF -308 G/A Polymorphism and Risk of Acne Vulgaris: A Meta-Analysis. PLoS ONE 9, (2014). • Delongui, F. et al. Association of tumor necrosis factor ß genetic polymorphism and sepsis susceptibility. Exp. Ther. Med. (2011). doi:10.3892/etm.2011.213 • Feng, R. N., Zhao, C., Sun, C. H. & Li, Y. Meta-analysis of TNF 308 G/A polymorphism and type 2 diabetes mellitus. PLoS One (2011). doi:10.1371/journal.pone.0018480 • Khan, S. et al. TNF-? -308 G?>?A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies. Scientific Reports 6, (2016). • Li, H. H. et al. Tumour Necrosis Factor-? Gene Polymorphism Is Associated with Metastasis in Patients with Triple Negative Breast Cancer. Sci. Rep. (2015). doi:10.1038/srep10244 • Ayhan, G. et al. Relation between inflammatory cytokine levels in serum and bronchoalveolar lavage fluid and gene polymorphism in young adult patients with bronchiectasis. J. Thorac. Dis. (2014). doi:10.3978/j.issn.2072-1439.2014.04.14 • Chen, S. et al. Associations between TNF-?-308A/G Polymorphism and Susceptibility with Dermatomyositis: A Meta-Analysis. PLoS ONE 9, (2014). • Chen, M. et al. Tumor Mecrosis Factor (TNF) -308G>A, Nitric Oxide Synthase 3 (NOS3) +894G>T polymorphisms and migraine risk: A meta-analysis. PLoS One (2015). doi:10.1371/journal.pone.0129372 • Lee, J. J. et al. Genetic polymorphism at codon 10 of the transforming growth factor-?1 gene in patients with alcoholic liver cirrhosis. Korean J. Hepatol. (2011). doi:10.3350/kjhep.2011.17.1.37 • Zeng, X., Zhang, L., Gu, H. & Gu, Y. Association between TNF-? -308 G/A polymorphism and COPD susceptibility: a meta-analysis update. International Journal of Chronic Obstructive Pulmonary Disease 1367 (2016). doi:10.2147/copd.s105394 • Li, M., Han, Y., Wu, T. T., Feng, Y. & Wang, H. B. Tumor Necrosis Factor Alpha rs1800629 Polymorphism and Risk of Cervical Lesions: A Meta-Analysis. PLoS One (2013). doi:10.1371/journal.pone.0069201 • Guo, X. F. et al. TNF-?-308 polymorphism and risk of digestive system cancers: A meta-analysis. World J. Gastroenterol. (2013). doi:10.3748/wjg.v19.i48.9461 • Ma, Zhang & Baloch. Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-? (TNF-?) in Major Depressive Disorder: A

Systematic Review. Int. J. Mol. Sci. (2016). doi:10.1016/j.cherd.2012.09.019

NEUROTRANSMITTER SNP References

COMT

• Bonifácio, M. J., Palma, P. N., Almeida, L. & Soares-Da-Silva, P. Catechol-O-methyltransferase and its inhibitors in Parkinson’s disease. CNS Drug Reviews (2007). doi:10.1111/j.1527-3458.2007.00020.x • Axelrod, J. O-methylation of epinephrine and other catechols in vitro and in vivo. Science (80-. ). (1957). doi:10.1126/science.126.3270.400 • Ulmanen, I. et al. Expression and intracellular localization of catechol O-methyltransferase in transfected mammalian cells. Eur. J. Biochem. (1997). doi:10.1111/j.1432-1033.1997.0452a.x • Stein, M. B., Fallin, M. D., Schork, N. J. & Gelernter, J. COMT polymorphisms and anxiety-related personality traits. Neuropsychopharmacology (2005). doi:10.1038/sj.npp.1300787 • Lotta, T. et al. Kinetics of Human Soluble and Membrane-Bound Catechol O-Methyltransferase: A Revised Mechanism and Description of the Thermolabile Variant of the Enzyme. Biochemistry (1995). doi:10.1021/bi00013a008 • Grossman, M. H., Emanuel, B. S. & Budarf, M. L. Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1?q11.2. Genomics (1992). doi:10.1016/0888-7543(92)90316-K • Golan, D. E., Armstrong, E. J. & Armstrong, A. W. Principles of pharmacology: the pathophysiologic basis of drug therapy. (Wolters Kluwer Health, 2017). • Wichers, M. et al. The catechol-O-methyl transferase Val158Met polymorphism and experience of reward in the flow of daily life. Neuropsychopharmacology (2008). doi:10.1038/sj.npp.1301520 • Diamond, A., Briand, L., Fossella, J. & Gehlbach, L. Genetic and Neurochemical Modulation of Prefrontal Cognitive Functions in Children. Am. J. Psychiatry (2004). doi:10.1176/appi.ajp.161.1.125 • Robinson, S., Goddard, L., Dritschel, B., Wisley, M. & Howlin, P. Executive functions in children with Autism Spectrum Disorders. Brain Cogn. (2009). doi:10.1016/j.bandc.2009.06.007 • Bruder, G. E. et al. Catechol-O-methyltransferase (COMT) genotypes and working memory: Associations with differing cognitive operations. Biol. Psychiatry (2005). doi:10.1016/j.biopsych.2005.05.010 • Chen, J. et al. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain. Am. J. Hum. Genet. (2004).

doi:10.1086/425589 • Tai, C. H. & Wu, R. M. Catechol-O-methyltransferase and Parkinson’s disease. Acta Medica Okayama (2002).

GAD1

• Bu, D. F. & Tobin, A. J. The exon-intron organization of the genes (gad1 and gad2) encoding two human glutamate decarboxylases (gad67and gad65) suggests that they derive from a common ancestral gad. Genomics (1994). doi:10.1006/geno.1994.1246 • Dirkx, R. et al. Targeting of the 67-kDa isoform of glutamic acid decarboxylase to intracellular organelles is mediated by its interaction with the NH2- terminal region of the 65-kDa isoform of glutamic acid decarboxylase. J. Biol. Chem. (1995). doi:10.1074/jbc.270.5.2241 • Giorda, R., Peakman, M., Tan, K. C., Vergani, D. & Trucco, M. Glutamic acid decarboxylase expression in islets and brain. The Lancet (1991). doi:10.1016/0140-6736(91)92781-V • KELLY, C. D. et al. Nucleotide sequence and chromosomal assignment of a cDNA encoding the large isoform of human glutamate decarboxylase. Ann. Hum. Genet. (1992). doi:10.1111/j.1469-1809.1992.tb01150.x • Demakova, E. V, Korobov, V. P. & Lemkina, L. M. Determination of gamma-aminobutyric acid concentration and activity of glutamate decarboxylase in blood serum of patients with multiple sclerosis. Klin. Lab. Diagn. (2003). • Asada, H. et al. Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to

seizures. Biochem. Biophys. Res. Commun. (1996). doi:10.1006/bbrc.1996.1898 • McHale, D. P. et al. A Gene for Autosomal Recessive Symmetrical Spastic Cerebral Palsy Maps to Chromosome 2q24-25. Am. J. Hum. Genet. (1999). doi:10.1086/302237

HTR2

• Kling, a et al. Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis. Ann. Rheum. Dis. (2008). doi:10.1136/ard.2007.074948 • Unschuld, P. G. et al. Polymorphisms in the serotonin receptor gene HTR2A are associated with quantitative traits in panic disorder. Am. J. Med. Genet.

Part B Neuropsychiatr. Genet. (2007). doi:10.1002/ajmg.b.30412 • Anton, R. F. et al. Pharmacogenomics. Nat. Genet. (2008). doi:10.1016/j.ejca.2015.06.122

IL1B

• Anton, R. F. et al. Pharmacogenomics. Nat. Genet. (2008). doi:10.1016/j.ejca.2015.06.122 • Licastro, F. et al. Gene polymorphism affecting alpha1-antichymotrypsin and interleukin-1 plasma levels increases Alzheimer’s disease risk. Ann. Neurol. (2000). doi:3.0.CO;2-G • Carter, K. W. et al. Association of Interleukin-1 gene

polymorphisms with central obesity and metabolic syndrome in a coronary heart disease population. Hum. Genet. (2008). doi:10.1007/s00439-008-0540-6

MAO-A

• Anton, R. F. et al. Pharmacogenomics. Nat. Genet. 16, 268–278 (2008). • Karmakar, A. et al. Pilot study indicate role of preferentially transmitted monoamine oxidase gene variants in behavioral problems of male ADHD probands. BMC Med. Genet. (2017). doi:10.1186/s12881-017-0469-5 • Kim, S. K. et al. Association study

between monoamine oxidase A (MAOA) gene polymorphisms and schizophrenia: Lack of association with schizophrenia and possible association with affective disturbances of schizophrenia. Mol. Biol. Rep. (2014). doi:10.1007/s11033-014-3207-5

MAO-B


• Bortolato, M., Godar, S. C., Davarian, S., Chen, K. & Shih, J. C. Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase b-deficient mice. Neuropsychopharmacology (2009). doi:10.1038/npp.2009.118 • Saura, J. et al. Increased monoamine oxidase b activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography. Neuroscience (1994). doi:10.1016/0306-4522(94)90311-5 • Riederer, P. & Laux, G. MAO-inhibitors in Parkinson’s Disease. Exp. Neurobiol. (2011). doi:10.5607/en.2011.20.1.1 • Mallajosyula, J. K., Chinta, S. J., Rajagopalan, S., Nicholls, D. G. & Andersen, J. K. Metabolic control analysis in a cellular model of elevated MAO-B: Relevance to parkinson’s disease. Neurotox. Res. (2009). doi:10.1007/s12640-009-9032-2 • Kumar, M. J. & Andersen, J. K. Perspectives on MAO-B in Aging and Neurological Disease: Where Do We Go From Here? Mol. Neurobiol. (2004). doi:10.1385/MN:30:1:077 • Ukraintseva, S. V., Arbeev, K. G., Michalsky, A. I. & Yashin, A. I. Antiaging treatments have been legally prescribed for approximately thirty years. in Annals of the New York Academy of Sciences (2004). doi:10.1196/annals.1297.014 • Edmondson, D. E., Binda, C. & Mattevi, A. Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B. Archives of Biochemistry and Biophysics (2007). doi:10.1016/j.abb.2007.05.006 • MAOB monoamine oxidase B [Homo sapiens (human)] - Gene - NCBI. National Center for Biotechnology Information Available at: https://www.ncbi.nlm.nih.gov/gene/4129. • Nolen, W. A., Hoencamp, E., Bouvy, P. F. & Haffmans, P. M. Reversible Monoamine Oxidase-A Inhibitors In Resistant Major Depression. Clinical Neuropharmacology 15, (1992). • Shih, J. C. & Chen, K. MAO-A and -B gene knock-out mice exhibit distinctly different behavior. Neurobiology (Budapest, Hungary). (1999). Available at: https://www.ncbi.nlm.nih.gov/pubmed/10591056. • Nagatsu, T. & Sawada, M. Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to Parkinson’s disease: possible implications of glial cells. J. Neural Transm. Suppl. (2006). doi:10.1007/978-3-211-33328-0_7 • Shih, J. C., Chen, K. & Ridd, M. J. MONOAMINE OXIDASE: From Genes to Behavior. Annu. Rev. Neurosci. (1999). doi:10.1146/annurev.neuro.22.1.197 • Miller, G. M. The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity. Journal of Neurochemistry (2011). doi:10.1111/j.1471-

4159.2010.07109.x

SLC6A4

• Landgren, S. et al. Genetic Variation of the Ghrelin Signaling System in Females With Severe Alcohol Dependence. Alcohol. Clin. Exp. Res. 34, 1519–1524 (2010). • Ait-Daoud, N. et al. Preliminary Evidence for cue-induced Alcohol Craving Modulated by Serotonin Transporter Gene Polymorphism rs1042173. Front. Psychiatry 3, 6 (2012). • Anton, R. F. et al. Pharmacogenomics. Nat. Genet. 16, 268–278 (2008). • Johnson, B. A. et al. Pharmacogenetic approach at the serotonin transporter gene as a method of reducing the severity of alcohol drinking. Am. J. Psychiatry 168, 265–275 (2011).


Documents

DOB: - GX Sciencesgxsciences.com/v/vspfiles/downloadables/Neuro_Psych... · 2018-12-19 · Neurological / Psych Neurotransmitters rs4680 COMT V158M +/+ Taurine, Choline, Trimethylglycine